Hydromechanical effects of continental ice sheets may involve considerably more than the widely recognized direct compression of overridden terrains by ice load. Lithospheric flexure, which lags ice advance and retreat, appears capable of causing comparable or greater stress changes. Together, direct and flexural loading may increase fluid pressures by tens of MPa in geologic units unable to drain. If so, fluid pressures in low-permeability formations subject to glaciation may have increased and decreased repeatedly during cycles of Pleistocene glaciation and can again in the future. Being asynchronous and normally oriented, direct and flexural loading presumably cause normal and shear stresses to evolve in a complex fashion through much or all of a glacial cycle. Simulations of fractured rock predict permeability might vary by two to three orders of magnitude under similar stress changes as fractures at different orientations are subjected to changing normal and shear stresses and some become critically stressed. Uncertainties surrounding these processes and their interactions, and the confounding influences of surface hydrologic changes, make it challenging to delineate their effects on groundwater flow and pressure regimes with any specificity. To date, evidence for hydromechanical changes caused by the last glaciation is sparse and inconclusive, comprising a few pressure anomalies attributed to the removal of direct ice load. This may change as more data are gathered, and understanding of relevant processes is refined.